This is one of the three interactive applications. Our previous pharmacologic studies of intravesical mitomycin C (MMC) therapy for patients with superficial bladder cancer suggest several treatment parameters which can be optimized to enhance the therapeutic efficacy and suggest several prognostic indicators to identify tumor subsets that are likely to be sensitive to MMC. this application has four independent and interactive aims. A.1. Compare therapeutic efficacy of a standard empirical intravesical MMC regimen to a pharmacology based optimized regimen. Patients with superficial bladder cancer, who have complete endoscopic resection of papillary tumor, will be randomized to the above treatment arms. Evaluation endpoints include tumor recurrence, tumor progression, and survival. Additionally, toxicity will be compared. A.2. Establish prognostic factors of patient response. Our data suggest that the different response of tumors is due to poor drug penetration into deep tissues and lower chemosensitivity of more aggressive tumors. Uni- and multivariate analysis will be used to examine the multiple prognostic factors with patient response and with the sensitivity of tumor explants to MMC. A.3. Provide specimens for companion interactive research project grants. Accompanying studies will examine tumor proliferative activity, MMC concentrations required to inhibit tumor proliferation, drug concentration in plasma, urine and bladder tissues, activity and gene expression of MMC activating enzymes. A.4. Correlate pharmacologic data of MMC with patient response. Using results from the interactive applications, a three-way comparison of these data will (a) indicate whether an effective MMC concentration was received, (b) allow assessment of inhibition of tumor proliferation by MMC, and (c) indicate the pharmacodynamic relationship between the drug concentration at target sites, the resulting antitumor effect, and the treatment outcome in patients. These correlations will provide insight on (a) the clinical significance of MMC-induced inhibition of tumor cell DNA synthesis, and (b) the role of expression of MMC activating enzymes in determining tumor response.